Mass Spectrometry in Drug Metabolism and Pharmacokinetics (PDF)

Preface vii About the Editor ix Contributors xi 1. Evolving Role of Mass Spectrometry in Drug Discovery and Development 1 Dil M. Ramanathan and Richard M. LeLacheur 2. Quantitative Bioanalysis in Drug Discovery and Development: Principles and Applications 87 Ayman El-Kattan, Chris Holliman, and Lucinda H. Cohen 3. Quadrupole, Triple-Quadrupole, and Hybrid Linear Ion Trap Mass Spectrometers for Metabolite Analysis 123 Elliott B. Jones 4. Applications of Quadrupole Time-of-Flight Mass Spectrometry in Reactive Metabolite Screening 159 Jose M. Castro-Perez 5. Changing Role of FTMS in Drug Metabolism 191 Petia A. Shipkova, Jonathan L. Josephs, and Mark Sanders 6. High-Resolution LC-MS-Based Mass Defect Filter Approach: Basic Concept and Application in Metabolite Detection 223 Haiying Zhang, Donglu Zhang, Mingshe Zhu, and Kenneth L. Ray 7. Applications of High-Sensitivity Mass Spectrometry and Radioactivity Detection Techniques in Drug Metabolism Studies 253 Wing W. Lam, Cho-Ming Loi, Angus Nedderman, and Don Walker 8. Online Electrochemical-LC-MS Techniques for Profiling and Characterizing Metabolites and Degradants 275 Paul H. Gamache, David F. Meyer, Michael C. Granger, and Ian N. Acworth 9. LC-MS Methods with Hydrogen/Deuterium Exchange for Identification of Hydroxylamine, N-Oxide, and Hydroxylated Analogs of Desloratadine 295 Natalia A. Penner, Joanna Zgoda-Pols, Ragu Ramanathan, Swapan K. Chowdhury, and Kevin B. Alton 10. Turbulent-Flow LC-MS: Applications for Accelerating Pharmacokinetic Profiling and Metabolite Identification 311 Joseph L. Herman and Joseph M. Di Bussolo 11. Desorption Ionization Techniques for Quantitative Analysis of Drug Molecules 341 Jason S. Gobey, John Janiszewski, and Mark J. Cole 12. MALDI Imaging Mass Spectrometry for Direct Tissue Analysis of Pharmaceuticals 359 Yunsheng Hsieh and Walter A. Korfmacher Index 383

Ragu Ramanathan received a B.Sc. in Chemistry from the University of Southern Mississippi and a Ph.D. in Physical Chemistry/Mass Spectrometry from the University of Florida. His graduate research focused on coupling of electrospray ionization (ESI) to Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. After spending three years as a postdoctoral research fellow with Professor Michael L. Gross at the Washington University, St. Louis, Missouri, Dr. Ramanathan managed the Center for Advanced Mass Spectrometry at the Analytical Bio-Chemistry Laboratories, Columbia, Missouri. In 1998, Dr. Ramanathan joined Schering-Plough Research Institute's (SPRI) Drug Metabolism and Pharmacokinetics (DMPK) Department and completed his tenure as a senior principal scientist in 2008. While at SPRI, Dr. Ramanathan was involved in the application of LC-MS for profiling and characterization of metabolites of drug candidates in the preclinical development and clinical stages. Dr. Ramanathan was with Pfizer Global Research and Development from 1999 to 2002 as a group leader of the Ann Arbor site biotransformation group. Dr. Ramanathan is currently an associate director at the Bristol-Myers Squibb, Co. and is responsible for elucidating biotransformation pathways of development drug candidates. Dr. Ramanathan's accomplishments include 35 peer-reviewed papers, 10 book chapters, and over 60 oral/poster presentations. He also served as a chairperson for the North Jersey ACS Mass Spectrometry Discussion Group and as a chairman for DMPK sessions of the American Society for Mass Spectrometry and Eastern Analytical Symposium meetings.

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